Acute liver abscess (AL) is a serious complication of inflammatory liver diseases and occurs against the background of decreased immunity, which occurs in diabetes mellitus (DM) [1-7]. This complication is characterized by rapid clinical development with chills, intoxication, and an increase in leukocytosis with a sharp shift to the left. Untimely treatment, without correction of blood sugar levels, develops a picture of sepsis with multiple organ failure [8]. The main principles of treatment of AP are timely diagnosis, antibacterial and detoxification therapy, opening and drainage of the source of infection, as well as correction of elevated blood sugar levels [9].

An urgent problem in assessing the effectiveness of various surgical approaches in the treatment of purulent-destructive processes in the liver occurring against the background of diabetes mellitus (DM) is the experimental formation of a diabetes model that would ensure a persistent increase in blood glucose levels and allow for objective studies to assess the characteristics of the course of various processes against the background of diabetes, and was not accompanied by high mortality in animals at the stage of development of diabetes.

Alloxan diabetes is the most established model for the development of diabetes mellitus in rats. "Alloxan (2,4,5,6-tetraoxohexahydropyrimidine) is an unstable pyrimidine derivative of uric acid with diabetogenic effects. In 1943, it was shown that the administration of this chemical compound to rabbits causes selective necrosis of the pancreatic islets with the subsequent development of classic symptoms of diabetes mellitus [10] Alloxan is a structural analogue of glucose, due to which it binds to the glucose transporter GLUT2 and selectively accumulates in pancreatic β-cells.

Further study of the biochemical mechanisms of action of alloxan showed the presence of a mechanism of destructive action of the latter through the generation of reactive oxygen species in a cyclic reaction with dialuric acid, which initiate the destruction of β-cells that have low antioxidant protection. Alloxan has a diabetogenic effect only when administered parenterally - intravenous, subcutaneous, intramuscular and intraperitoneal [11]. The effective dose depends on the animal species, route of administration, nutritional status and the type of diabetes being induced.

The successful creation of a model of diabetes in laboratory animals allows us to conduct objective studies to evaluate the effectiveness of various methods of surgical treatment of experimental AL.

Experimental studies were carried out in the laboratory of experimental surgery of the State Institution "Republican Specialized Scientific and Practical Medical Center of Surgery named after academician V. Vakhidov" on 54 white outbred rats of both sexes weighing 240-310g. The animals were kept in cages of 2 individuals in a vivarium equipped with supply and exhaust ventilation with an air temperature of 22-23o C. Nutrition was provided by taking a balanced diet including dry food and vitamins. Water was provided in unlimited quantities. Before performing the experiments, the animals were kept without food for 12 hours. All manipulations were performed in accordance with the requirements for humane treatment of experimental animals (Strasbourg 1986).Under experimental conditions, a model of acute AL was tested on rats by placing a gauze implant soaked in feces obtained from the lumen of the cecum into the interlobar space of the liver. The presence of anaerobic flora contributes to the rapid development of a purulent-necrotic process involving the liver parenchyma and the formation of a limited abscess within a day after the formation of the model.In rats, against the background of alloxan diabetes, a model of acute liver abscess was formed on the 3rd day after the last injection of alloxan and the animals were in a satisfactory general condition. To evaluate the effectiveness of treatment of AL against the background of diabetes in an experiment, it is advisable to simulate AL in a rat 3 days after the last administration of alloxan, and perform surgical treatment for acute AL one day after implantation of the infectious source in the liver.In the control group of animals with AL against the background of alloxan-induced diabetes, surgical treatment consisted of laparotomy under general anesthesia with sevaflurane vapor, removal of the sewn-in infected implant, visualization of a limited purulent cavity in the liver measuring up to 0.7 cm in diameter, covered with fibrin and necrotic masses. The abscess cavity was treated by evacuation of pus and sanitation with a solution of dioxidine 2.0% - 2.0, administration of 0.5 ml of a 10% solution of levofloxacin, after which the abdominal wall was sutured with a continuous double-row suture.In the experimental group of animals with acute AL against the background of alloxan-induced diabetes, surgical treatment consisted of laparotomy under general anesthesia with sevaflurane vapor, removal of the sewn-in infected implant, visualization of a limited purulent cavity in the liver, covered with fibrin and necrotic masses. The abscess cavity was treated by evacuation of pus and sanitation of the cavity with a solution of dioxidine 2.0% - 2.0, administration of 0.5 ml of a 10% solution of levofloxacin, followed by irradiation with a NEL device Matrix with a wavelength of 337 nm with a power of 5 mW for 1 minute, suturing the abdominal wall continuous double-row seam. The difference between the method is that levofloxacin is an antibiotic with photosensitizing properties, the activity of which manifests itself after irradiation with ultraviolet rays. As a result, its effectiveness increases and the spectrum of antimicrobial effects expands.

Control group. To reduce the load on the pancreas, the rats were put on a special diet: carbohydrates were limited in the diet, protein intake was increased (buckwheat porridge, dried fruits, vegetables, legumes and white meat). On the next day after the operation, death occurred in 2 individuals. At autopsy, the presence of cloudy effusion in the abdominal cavity and diffuse peritonitis was determined. Congestion of internal organs. Sepsis.

The remaining animals move around the cage, take food in limited quantities, and drink water. The coat is dull. Nose and tongue tend to be dry. From this group of animals, 3 were removed from the experiment by administering an anesthetic drug; blood was previously taken from a vein for biochemical tests. When opening the abdominal cavity, an increase in the size of the liver, an infiltrate involving the omentum, stomach, and intestines with loose adhesions were determined. There are fibrin deposits on the anterior surface of the liver, indicating the presence of a purulent cavity in the liver. Internal organs are full-blooded and congested.

The intestines are distended, the stomach is also distended with contents and a large amount of air. The abscess cavity measures 8x8 mm and is covered with necrotic plaque (Figure 1). A biopsy was taken from the liver, spleen and pancreas.

Figure 1: 1 Day after the Formation of an Abscess in the Liver. Purulent-Necrotic Liver Abscess, Sepsis.

Changes in the liver were pronounced and manifested themselves as venous stasis, dilation and blood filling of sinusoidal capillaries, destruction of hepatocytes, formation of fibrin thrombi, and leukocyte infiltration. Central venous congestion, congestion and dilatation of hepatic sinusoids, and inflammation of the portal tracts were also noted (Figure 2).

Figure 2: Control. 1 Day after the Formation of a Liver Abscess against the Background of Diabetes Mellitus. Hematoxylin and Eosin Staining. Ok10xob40.

On the 3rd day after surgery, animals in the control group moved freely around the cage, but their activity was limited. Physiological functions are normal; they take food and water.

By overdose of a narcotic drug, 2 individuals were removed from the experiment. At autopsy, the abdominal cavity is clean, there is no effusion. The liver is enlarged, swollen, white spots appear on the front surface, indicating the presence of a purulent cavity.

The liver is surrounded by dense adhesions with the omentum, stomach, and anterior abdominal wall. When separating the adhesions, the abscess cavity in the liver was opened. The purulent cavity is 0.7 cm in diameter, the contents are scanty with an odor (Figure 3-4). The walls of the cavity are covered with fibrin plaque and necrotic masses. The liver tissue is infiltrated, loose, gray in color. The intestines and stomach are moderately dilated, there are no signs of intestinal obstruction.

Figure 3: Control. 3 Days after Opening of the Abscess. Purulent-Necrotic Cavity in the Liver.

Figure 4: Control. Liver 3 Days after Sanitation of a Liver Abscess Due to Diabetes Mellitus. Hematoxylin and Eosin Staining. Ok10xob40.

On the 7th day after opening the abscess against the background of alloxan diabetes, the rats actively move around the cage and resist when trying to pick it up. The coat begins to return to its normal state. Nose and tongue are moist.

When the abdominal cavity is opened, there is no effusion. The liver is enlarged, infiltrated, edematous pronounced adhesions to surrounding tissues. Fibrin plaque is visible along the anterior surface of the left lobe of the liver. When separating adhesions by sharp means, the abscess cavity was opened.

There is no discharge, there is no smell. The cavity measures 6-8 mm in diameter, the walls are covered with fibrin and necrotic masses. Liver tissue was taken for histological examination (Figure 5).

Figure 5: Control. 7 Days after Opening and Sanitation of the Abscess. Infiltrate, Adhesions in the Liver Area. Abscess Cavity of Irregular Shape with Necrotic Tissue, Fibrin.

Prenoplastic glycogen-storing foci of hepatocytes (HS-foci), as well as signs of toxic damage to the parenchyma and inflammatory proliferations: granulomas and nodules of small cell infiltration and proliferation (MC nodules) were recorded on paraffin sections. (Figure 6).

Figure 6: Control. Liver. 7 Days after Sanitation of the Liver Abscess Cavity against the Background of Diabetes. Hematoxylin and Eosin Staining. Ok10xob40.

On the 14th day after surgery, no changes were observed in the condition of the animals. The wound healed by primary intention. Under anesthesia, blood was taken from the animals for laboratory tests. When the abdominal cavity is opened, the infiltrate and enlargement of the liver remain. Dense adhesions of the liver to surrounding tissues are determined. When the liver is isolated from the adhesions, the infiltrated liver tissue is torn. When opening the residual cavity, there is no abscess discharge, the smell is not detected. The abscess cavity is covered with fibrin, necrotic plaque is dark gray in color. When fibrin films are separated, young granulation tissue is detected in some places. The abscess cavity is 5-7 mm in diameter and irregular in shape.

In the centrilobular zones of the liver parenchyma, necrosis of hepatocytes and leukocyte infiltration were detected. Also in this zone, single Councilman's corpuscles were found. In addition, blood filling of the central veins and some portal tracts and the release of blood into the liver parenchyma were detected.On the 30th day after surgery, changes in the condition of the animals are hardly noticeable from healthy individuals. The wound on the anterior abdominal wall has completely healed, and the fur has been restored.

Under general anesthesia, blood was drawn for laboratory tests. When opening the abdominal cavity, the liver is moderately enlarged in the left half, where compaction is detected at the site of the formed abscess. There are dense adhesions with surrounding tissues. When the layers of the liver are separated, the abscess cavity remains 2x4 mm in size, the walls are covered with a white fibrin coating. Liver infiltration happens only along the edge of the residual abscess cavity (Figure 7). When fibrin is separated, granulation tissue is visualized, which is actively bleeding.

Figure 7: Control 30 Days. Adhesive Process in the area of ??Liver Abscess. The Liver Retains a Small Cavity Covered with Fibrin.

In zone III of the hepatic acinus, large droplet vacuolization, infiltration of inflammatory cells, balloon degeneration, necrosis of hepatocytes, apoptotic bodies, centrilobular necrosis, which sometimes extended into centrocentral bridging necrosis, were detected (Figure 8). Fine-droplet vacuolization was observed in zones I and II of the acinus, but the radial arrangement of the hepatocyte beams was preserved. There was weak cellular infiltration in some portal tracts.

Figure 8: Control. Liver. 30 Days after Rehabilitation of Ap Due to Diabetes. Hematoxylin and Eosin Staining. Ok10xob40.

On the 45th day after surgery, the condition of the animals approaches that of healthy individuals. At autopsy, the liver is moderately enlarged in the left half, where compaction is determined at the site of the formed abscess. There are dense adhesions with surrounding tissues. When the layers of the liver are separated, the abscess cavity remains 3x3 mm in size, the walls are covered with a white fibrin coating including the case where Liver infiltration only along the edge of the residual abscess cavity. When fibrin is separated, granulation tissue is visualized, which is actively bleeding.

When opening the abdominal cavity one day after the operation, swelling, infiltration in the liver area, and the surface of the liver with a white coating were determined, indicating the presence of a purulent cavity. Internal organs are full-blooded and congested. The intestines will be brought in, the stomach will also be distended with contents and a large amount of air. The abscess cavity is 7x7 mm, covered with necrotic plaque. A biopsy was taken from the liver, spleen and pancreas.

On the 3rd day after surgery, the animals move freely around the cage and are active. Physiological functions are normal; they take food and water.

By overdose of a narcotic drug, 3 individuals were removed from the experiment. At autopsy, the abdominal cavity is clean, there is no effusion. The liver is enlarged, swollen, white spots appear on the front surface, indicating the presence of a purulent cavity.

The liver is surrounded by dense adhesions with the omentum, stomach, and anterior abdominal wall. When separating the adhesions, the abscess cavity in the liver was opened. The cavity is 4-5 mm in diameter, without contents (Figure 9). The walls of the cavity are covered with a white fibrin coating. The liver tissue is infiltrated at the border with the residual cavity.

Figure 9: Experience. 3 Days after Opening of the Abscess. There is a Residual Cavity in the Liver with Necrotic Plaque and Fibrin.

On the 7th day after surgery, no changes were observed in the condition of the animals. The wound healed by primary intention. Under anesthesia, blood was taken from the animals for laboratory tests. When the abdominal cavity is opened, the infiltrate and enlargement of the liver remain. Dense adhesions of the liver to surrounding tissues are determined. When the liver is isolated from the adhesions, the infiltrated liver tissue is torn.

When opening the residual cavity, there is no abscess discharge, the smell is not detected. The abscess cavity is covered with fibrin, necrotic masses are not visually detected. When fibrin films are separated, young granulation tissue is detected in some places. The abscess cavity is 5 mm in diameter and irregular in shape. A biopsy was taken from the liver, spleen and pancreas.

Histological examination in the 3rd zone of the hepatic acini did not reveal signs of necrobiosis in most cases; however, hepatocytes with hydropic and balloon degeneration were rarely encountered. Inflammatory infiltration was present around the central veins. The radial arrangement of hepatocyte trabeculae was observed in all rats of this group. As in the previous group, signs of reparative and restoration processes were found: binuclear and polyploid hepatocytes were often found.

On the 14th day after the operation, the animals’ condition showed little noticeable differences from healthy animals. The wound has completely healed and the fur has been restored. Under general anesthesia, blood was drawn for laboratory tests. When the abdominal cavity was opened, the liver significantly decreased in size and reached normal values. There are adhesions with surrounding tissues. When the layers of the liver are separated, the abscess cavity remains 2x4 mm in size, the walls are covered with a white fibrin coating (Figure 10). Liver infiltration only along the edge of the residual abscess cavity. Organ tissue was taken for histological and examination.

The Gleason capsule of the liver is thin without any deviations from the norm. The trabecular and lobular structure of the hepatic parenchyma is preserved. It consists of liver cells radially oriented from the central veins. Liver cells intensively perceived color; most contain 2 nuclei with fine-grained chromatin diffusely located (Figure 11). Protein granularity was found in the cytoplasm. Sinusoidal capillaries of normal size with single blood cells or blood filling. Contains numerous Kupffer cells. In some places, mild lymphoid cell infiltration of the portal tracts is found, sometimes around the central veins.

 Figure 10: Experience 14 Days. Adhesions with the Lower Surface of the Liver. There is a Small Cavity in the Liver without Necrotic Plaque.

Figure 11: Experience. Liver - 14 Days after Surgery. Hematoxylin and Eosin Staining. Ok10xob40.

On the 30th day after surgery, only adhesions to the lower surface of the liver were detected.

According to laboratory tests, in the control group of animals, leukocytosis was observed within 30 days, while in the experimental group, normalization of indicators occurred by 21 days after surgical treatment (Figure 12).

Figure 12: Average values ??of Leukocyte Levels in Experimental Animals.

Note: The arrow indicates indicators with a significant (p<0.05) difference between the experiment and control.

To summarize, we can conclude that liver abscesses against the background of diabetes occur with complications in the form of sepsis and a high probability of death. Removing the source of the abscess and sanitizing the cavity does not guarantee a quick recovery of the animal despite a decrease in intoxication and restoration of physical activity. Carrying out laser exposure with photodynamic activation of a levofloxacin solution contributes to a full antimicrobial effect, and laser radiation has a beneficial effect on the healing processes of liver abscess.

Conclusion. When modeling acute purulent AL, a technique was used using as an initiating principle a gauze ball measuring 7 mm in diameter, impregnated with the microflora of feces of the cecum at the rate of 10 mg diluted in 1.0 ml of physiological solution which was fixed between the lobes of the liver. The next day after implantation, a typical picture of intoxication, sepsis and the formation of a destructive limited focus in the liver was observed. Subsequent observations made it possible to establish that without treatment, on days 2-3 after surgery, almost all operated animals died from progressive intoxication and sepsis.

An increase in the total number of leukocytes, lymphocytic and granulocytic fractions in the peripheral blood of diabetic rats indicates the activation of nonspecific and specific immune reactions that cause autoimmune aggression and inflammation in the liver and other organs. The inflammatory process is more pronounced in the liver of rats on day 1, which is consistent with the detected higher ALT activity in this group compared to day 45. The absence of significant changes in the fraction of medium cells in the blood may be due to the transition to the pancreas, liver and other organs of a significant part of monocytes, which differentiate into macrophages in the organs.

The next day after implantation, the source of infection was removed with sanitation of the abscess cavity using a 2% solution of dioxidine and the introduction of 0.5 ml of a 10% solution of levofloxacin into the abscess lumen. In the experimental group of animals, after administration of a levoflocycline solution, NEL irradiation was performed with a wavelength of 337 nm, a power of 5.0 mW, and a duration of 1 min.

In the control group of animals with alloxan diabetes, the disease was severe with complications - death occurred in 2 animals on the 1st day after surgery. According to autopsy data, the dynamics of healing proceeded slowly, the abscess cavity with detritus and fibrin deposits persisted for 45 days after surgery, although the general condition of the animals returned to normal already on days 14-21. In the experimental group of animals, recovery occurred fast.

So, on the 3rd day, the animals actively moved around the cage; the restoration of physical activity occurred on the 7th day after the operation. The abscess cavity healed faster. By day 7, the abscess cavity was cleared of detritus. The size of the destruction focus decreased. Fibrin overlays remained for 14 days after surgery. Cleansing and healing of the abscess cavity occurred 21 days after surgery.

1. Khim G, Em S, Mo S, Townell N. Liver abscess: diagnostic and management issues found in the low resource setting. Br Med Bull. 2019; 132: 45-52.
2. Li W, Chen H, Wu S, Peng J. A comparison of pyogenic liver abscess in patients with or without diabetes: a retrospective study of 246 cases. BMC Gastroenterol. 2018; 18: 144.
3. Babadjanov AK, Yakubov FR, Ruzmatov PY, Sapaev DS. Epidemiological aspects of echinococcosis of the liver and other organs in the Republic of Uzbekistan. Parasite Epidemiol Control. 2021; 15.
4. Sapaev DS, Yakubov FR, Yakhshiboev SS, Evaluation of the factors influencing the choice of laparoscopic echinococcectomy in liver echinococcosis (LE) and its impact on postoperative outcomes. Experimental Parasitology. 2023; 248.
5. Yakubov FR, Sapaev DS, Surgical treatment of liver echinococcosis. J Med Life.  2022; 15: 1409-1414.  
6. Ruzibaev RYu, Kuryazov BN, Sapaev DSh, Yakubov FR, Rustamov PYu, Babadzhanov AR. Modern Estimation of the Problems of Diagnosis and Surgical Treatment of Echinococcosis. ?. ?. ????????. 2019; 14: 134-139.
7. Sapaev DSh, RUZIBAEV RYU, YAKUBOV FR. Modern Diagnostics and Surgical Treatment of Supupent Liver Echinococcosis. Infections In Surgery. 2018; 16: 10-11.
8. Liu L, Chen W, Lu X, Zhang K, Zhu C. Pyogenic Liver Abscess: A Retrospective Study of 105 Cases in an Emergency Department from East China. The Journal of Emergency Medicine. 2017; 52: 409-416.
9. Wang TY, Lai HC, Chen HH, Wang ML, Hsieh MC, et al. Pyogenic Liver Abscess Risk in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study. Front Med (Lausanne). 2021; 8.
10. Bibik EYu, Krivokolysko SG, Dostsenko VV, Tilchenko DA, Frolov KA, et al. Comparative Characteristics of The Influence of a New Pyridine Derivative on The Course of Diabetes Mellitus in Four Experimental Models. Vestnik VolgGMU. 2019; 30: 42-46.
11. Glybochko PV, Fomin VV, Moiseev SV. Outcomes in patients with severe course COVID-19 hospitalized for respiratory support in intensive care units. Clinical Pharmacology and Therapy. 2020; 29: 25-36.